The lysis of gram-negative bacteria
causes them to release lipopolysaccharide (LPS; endotoxin) from the outer membrane
of their cell wall. The LPS binds to a LPS-binding protein circulating in the
blood and this complex, in turn, binds to a receptor molecule (CD14)
found on the surface of body defense cells called macrophages.This
triggers the macrophages to release various defense regulatory chemicals called
cytokines, including IL-1, IL-6, IL-8, TNF-alpha, and PAF. The cytokines then
bind to cytokine receptors on target cells stimulating the production of inflammatory
mediators such as prostaglandins and leukotreins as well as activating both
the complement pathways and the coagulation pathway. Excessive production of
clotting factors may lead to ARDS and DIC while an overproduction of prostaglandins,
leukotreins, and complement proteins can damage the vascular endothelium resulting
in shock and MOSF. (LPS, lipopolysaccharide; IL-1, interleukin-1; IL-6, interleukin-6;
IL-8, interleukin-8, TNF-alpha, tumor necrosis factor-alpha; PAF, platelet-activating
factor; ARDS, acute respiratory distress syndrome; DIC, disseminated intravascular
coagulation; MOSF, multiple organ system failure.)